Everolimus Combined With PD-1 in Advanced Colorectal Cancer Patients

NCT06301386 | Not Yet Recruiting Phase 2

• 1 other identifier: EVOLUTION
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of this clinical trial is to learn about efficacy of Everolimus in combination with PD-1 in patients with locally advanced and advanced colorectal cancer that cannot be R0 resected. The main question is to explore the survival time, safety and tolerability of the treatment. At the same time, the correlation between biomarkers (including PD-L1 expression, tumor mutation load, lymphocyte subpopulation, cytokines, TCR, intestinal microbes, and others) and the efficacy and drug resistance mechanism will be analyzed, so as to provide reference for the subsequent guidance of the screening of benefit groups.

Conditions

Colon Cancer

Keywords

mTOR inhibitor; immunotherapy

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR)

  The proportion of participants whose best outcome is complete remission or partial remission

  2 year

Secondary Outcomes (4)

• progression-free survival (PFS）

  2 year

• overall survival (OS)

  2 year

• disease control rate (DCRs)

  2 year

• advert events

  2 year

Study Arms (1)

Everolimus in combination with PD-1

EXPERIMENTAL

Patients will be treated with Everolimus and PD-1

Drug: Everolimus; Drug: PD-1

Interventions

Everolimus DRUG

Patients receive oral everolimus once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

Everolimus in combination with PD-1

PD-1 DRUG

200mg intravenously every 3 weeks (Q3W), was administered until the occurrence of unacceptable toxic effects, or disease progression, withdrawal of consent, or withdrawal as judged by the investigator.

Everolimus in combination with PD-1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old, both sexes;
• Patients with histologically or cytologically confirmed locally advanced and advanced colorectal cancer that cannot be R0 resected;
• Recist1.1-defined disease progression or intolerance to prior standard therapy during or after standard therapy. Standard therapy was required to include all the following agents: fluorouracilines, chemotherapy agents such as irinotecan, and oxaliplatin, with or without an anti-VEGF monoclonal antibody (e.g., bevacizumab). Left-sided KRAS/NRAS/BRAF wild-type subjects received combined anti-EGFR mAb (cetuximab or panitumumab).
• Before enrollment, the tumor tissue was PTEN mutations;
• Patients with ECOG score of 0-1 and expected survival time ≥3 months, patients who can cooperate to observe adverse reactions and efficacy;
• At least one measurable tumor lesion according to RECIST 1.1 criteria;
• Good organ function:
• neutrophil ≥1.5\*109/L; Platelet ≥100\*109/L; Hemoglobin ≥9g/dl; Serum albumin ≥3g/dl;
• Thyroid stimulating hormone (TSH) ≤ 1 times the upper limit of normal, T3 and T4 in the normal range;
• bilirubin ≤ 1.5 times the upper limit of normal value; ALT and AST≤ 2 times the upper limit of normal;
• Serum creatinine ≤ 1.5 times the upper limit of normal, creatinine clearance ≥60ml/min;
• International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times the upper limit of the normal range, unless the patient is receiving anticoagulant therapy and the PT value is within the intended range for anticoagulant therapy;
• Activated partial thromboplastin time (aPTT) ≤ 1.5 times the upper limit of normal;
• There were no serious concomitant diseases that could make the survival time less than 5 years;
• Negative pregnancy test in female subjects (for female patients of childbearing potential); Infertile female patients;

You may not qualify if:

• Pathological diagnosis of other intestinal tumors, such as gastrointestinal stromal tumor;
• Prior treatment with PD-1 antibody;
• Prior treatment with mTOR inhibitor;
• Previous or concurrent history of other malignant tumors, excluding adequately treated non-melanoma skin cancer, cervical carcinoma in situ and thyroid papillary carcinoma;
• Active autoimmune disease, history of autoimmune disease (such as interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes); It does not include autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone; Type I diabetes on stable doses of insulin; Vitiligo or cured childhood asthma/allergy without any intervention in adulthood;
• A history of immunodeficiency, including HIV positive, other acquired or congenital immunodeficiency diseases, or organ transplantation or allogeneic bone marrow transplantation;
• Contraindications to antiangiogenic drugs (such as active bleeding, gastrointestinal bleeding, hemoptysis, etc.);
• History of interstitial lung disease (excluding radiation pneumonitis without steroid treatment) and non-infectious pneumonia;
• Patients with active pulmonary tuberculosis infection detected by medical history or CT examination, or with a history of active pulmonary tuberculosis infection within 1 year before enrollment, or with a history of active pulmonary tuberculosis infection more than 1 year before enrollment but without regular treatment;
• The subject has active hepatitis B (HBV DNA ≥2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive and HCV-RNA above the detection limit of the assay)
• Severe cardiopulmonary and renal dysfunction;
• Have hypertension that is not well controlled with antihypertensive medication (systolic blood pressure ≥140mmHg or diastolic blood pressure ≥90mmHg);
• A history of psychotropic substance abuse, alcohol or drug abuse;
• Other factors that may affect subject safety or trial compliance as judged by the investigator. Severe medical conditions requiring concomitant treatment (including mental illness), serious laboratory abnormalities, or other family or social factors.

Sponsors & Collaborators

• Fudan University: lead
• Anyang Tumor Hospital: collaborator

Study Sites (2)

Anyang Tumor Hospital

Anyang, Henan, China

Location

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

Location

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

Everolimus

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Dawei Li, PhD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dawei Li, PhD

CONTACT

+8613774201693; li_dawei@fudan.edu.cn

Yanjun Wang, PhD

CONTACT

+8613837266702; m13837266702@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 3, 2024
• First Posted: March 8, 2024
• Study Start: April 1, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 8, 2024

Record last verified: 2024-03

Locations

CN (2)